NZ540275A - Calcilytic compounds and their use as calcium receptor antagonists - Google Patents
Calcilytic compounds and their use as calcium receptor antagonistsInfo
- Publication number
- NZ540275A NZ540275A NZ540275A NZ54027503A NZ540275A NZ 540275 A NZ540275 A NZ 540275A NZ 540275 A NZ540275 A NZ 540275A NZ 54027503 A NZ54027503 A NZ 54027503A NZ 540275 A NZ540275 A NZ 540275A
- Authority
- NZ
- New Zealand
- Prior art keywords
- indan
- phenyl
- hydroxy
- dimethyl
- propoxy
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 54
- 230000001126 calcilytic effect Effects 0.000 title abstract description 16
- 229940123613 Calcium receptor antagonist Drugs 0.000 title description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 108090000445 Parathyroid hormone Proteins 0.000 claims abstract description 12
- 230000002159 abnormal effect Effects 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 150000002367 halogens Chemical class 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 10
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 7
- 208000035475 disorder Diseases 0.000 claims abstract description 6
- 210000002966 serum Anatomy 0.000 claims abstract description 5
- 125000001424 substituent group Chemical group 0.000 claims abstract description 5
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 4
- 208000010392 Bone Fractures Diseases 0.000 claims abstract description 4
- 206010017076 Fracture Diseases 0.000 claims abstract description 4
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 4
- 230000035876 healing Effects 0.000 claims abstract description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 4
- 239000011707 mineral Substances 0.000 claims abstract description 4
- 230000004079 mineral homeostasis Effects 0.000 claims abstract description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 4
- 208000037147 Hypercalcaemia Diseases 0.000 claims abstract description 3
- 241000124008 Mammalia Species 0.000 claims abstract description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 3
- 102000003982 Parathyroid hormone Human genes 0.000 claims abstract description 3
- 201000011510 cancer Diseases 0.000 claims abstract description 3
- 230000000148 hypercalcaemia Effects 0.000 claims abstract description 3
- 208000030915 hypercalcemia disease Diseases 0.000 claims abstract description 3
- 230000036210 malignancy Effects 0.000 claims abstract description 3
- 201000008968 osteosarcoma Diseases 0.000 claims abstract description 3
- 239000000199 parathyroid hormone Substances 0.000 claims abstract description 3
- 229960001319 parathyroid hormone Drugs 0.000 claims abstract description 3
- 208000028169 periodontal disease Diseases 0.000 claims abstract description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 68
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
- 238000002360 preparation method Methods 0.000 claims description 32
- 239000007787 solid Substances 0.000 claims description 28
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 20
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 8
- -1 {3-Bromo-4-[(R)-2-hydroxy-3-(2-indan-2-yl-1,1 -dimethyl-ethylamino)-propoxy] -phenyl}-propionic acid ethyl ester Chemical compound 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
- 150000003840 hydrochlorides Chemical class 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- UENUVEDCNCZXEM-ZMBIFBSDSA-N 3-[2-chloro-5-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoic acid;hydrochloride Chemical compound Cl.C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC=C(Cl)C(CCC(O)=O)=C1 UENUVEDCNCZXEM-ZMBIFBSDSA-N 0.000 claims description 2
- WDQLTXBRIIQPTL-VEIFNGETSA-N 3-[4-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-2,3-difluorophenyl]propanoic acid;hydrochloride Chemical compound Cl.C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC=C(CCC(O)=O)C(F)=C1F WDQLTXBRIIQPTL-VEIFNGETSA-N 0.000 claims description 2
- RCAWSMITRJKBGA-VZYDHVRKSA-N 5-[3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4,5-difluorophenyl]pentanoic acid;hydrochloride Chemical compound Cl.C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC(CCCCC(O)=O)=CC(F)=C1F RCAWSMITRJKBGA-VZYDHVRKSA-N 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- NAWCUHBFTPVIKY-ZMBIFBSDSA-N 3-[4-bromo-3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoic acid;hydrochloride Chemical compound Cl.C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC(CCC(O)=O)=CC=C1Br NAWCUHBFTPVIKY-ZMBIFBSDSA-N 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- BQGSCEAKPBWIDI-VEIFNGETSA-N 3-[3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4,5-difluorophenyl]propanoic acid;hydrochloride Chemical compound Cl.C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC(CCC(O)=O)=CC(F)=C1F BQGSCEAKPBWIDI-VEIFNGETSA-N 0.000 claims 1
- MPGSHUYHOPADTQ-ZMBIFBSDSA-N 3-[3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4-fluorophenyl]propanoic acid;hydrochloride Chemical compound Cl.C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC(CCC(O)=O)=CC=C1F MPGSHUYHOPADTQ-ZMBIFBSDSA-N 0.000 claims 1
- LIHPVWIAWJWGJQ-OAQYLSRUSA-N 3-[3-bromo-4-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoic acid Chemical compound C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC=C(CCC(O)=O)C=C1Br LIHPVWIAWJWGJQ-OAQYLSRUSA-N 0.000 claims 1
- BXKXKXHUFYKFHW-OAQYLSRUSA-N 3-[3-chloro-4-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoic acid Chemical compound C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC=C(CCC(O)=O)C=C1Cl BXKXKXHUFYKFHW-OAQYLSRUSA-N 0.000 claims 1
- DUGUZHJXUMKELM-VZYDHVRKSA-N 5-[2,3-dichloro-4-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]pentanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H](O)CNC(C)(CC1CC2=CC=CC=C2C1)C)OC1=CC=C(CCCCC(O)=O)C(Cl)=C1Cl DUGUZHJXUMKELM-VZYDHVRKSA-N 0.000 claims 1
- NDUPDOJHUQKPAG-UHFFFAOYSA-N Dalapon Chemical compound CC(Cl)(Cl)C(O)=O NDUPDOJHUQKPAG-UHFFFAOYSA-N 0.000 claims 1
- 238000006298 dechlorination reaction Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- VDNMWPOVPRGCCA-QAOXVKOZSA-N ethyl 2-[2,3-dichloro-4-[(2R,3R)-4-[[1-(2,3-dihydro-1H-inden-2-yl)-2-methylpropan-2-yl]amino]-3-hydroxybutan-2-yl]oxyphenyl]propanoate hydrochloride Chemical compound CCOC(=O)C(C)C1=C(C(=C(C=C1)O[C@H](C)[C@@H](CNC(C)(C)CC2CC3=CC=CC=C3C2)O)Cl)Cl.Cl VDNMWPOVPRGCCA-QAOXVKOZSA-N 0.000 claims 1
- WFCBOSWUFNSLRN-JOCHJYFZSA-N ethyl 3-[2,4-dichloro-5-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound C1=C(Cl)C(CCC(=O)OCC)=CC(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1Cl WFCBOSWUFNSLRN-JOCHJYFZSA-N 0.000 claims 1
- SOCOIINUQRAGMY-VZYDHVRKSA-N ethyl 3-[3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4,5-difluorophenyl]propanoate;hydrochloride Chemical compound Cl.CCOC(=O)CCC1=CC(F)=C(F)C(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 SOCOIINUQRAGMY-VZYDHVRKSA-N 0.000 claims 1
- VBFBLNNOVYBQFU-XMMPIXPASA-N ethyl 3-[3-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(OC[C@H](O)CNC(C)(C)CC2CC3=CC=CC=C3C2)=C1 VBFBLNNOVYBQFU-XMMPIXPASA-N 0.000 claims 1
- WEXICWDSWSUXQQ-HSZRJFAPSA-N ethyl 3-[3-bromo-4-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoate Chemical compound BrC1=CC(CCC(=O)OCC)=CC=C1OC[C@H](O)CNC(C)(C)CC1CC2=CC=CC=C2C1 WEXICWDSWSUXQQ-HSZRJFAPSA-N 0.000 claims 1
- FTJVOWUWKFMRMW-GJFSDDNBSA-N ethyl 5-[2,3-dichloro-4-[(2r)-3-[[1-(2,3-dihydro-1h-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]pentanoate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.ClC1=C(Cl)C(CCCCC(=O)OCC)=CC=C1OC[C@H](O)CNC(C)(C)CC1CC2=CC=CC=C2C1 FTJVOWUWKFMRMW-GJFSDDNBSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 89
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 70
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 67
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 239000000047 product Substances 0.000 description 38
- 239000000243 solution Substances 0.000 description 35
- 235000019439 ethyl acetate Nutrition 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 150000002148 esters Chemical class 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- 229910001868 water Inorganic materials 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- 239000010410 layer Substances 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
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- 239000012267 brine Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 102000013830 Calcium-Sensing Receptors Human genes 0.000 description 10
- 108010050543 Calcium-Sensing Receptors Proteins 0.000 description 10
- 150000002118 epoxides Chemical class 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 9
- 102100036893 Parathyroid hormone Human genes 0.000 description 9
- 239000011575 calcium Substances 0.000 description 9
- 229910052791 calcium Inorganic materials 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
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- 230000028327 secretion Effects 0.000 description 8
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- 238000001816 cooling Methods 0.000 description 7
- ZECGNJSXCCKHDX-UHFFFAOYSA-N ethyl 3-(3-hydroxyphenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=CC(O)=C1 ZECGNJSXCCKHDX-UHFFFAOYSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
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- AIHIHVZYAAMDPM-MRVPVSSYSA-N [(2r)-oxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OC[C@@H]2OC2)=C1 AIHIHVZYAAMDPM-MRVPVSSYSA-N 0.000 description 4
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- 125000004432 carbon atom Chemical group C* 0.000 description 4
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- YYFIGOPUHPDIBO-UHFFFAOYSA-N propanoic acid;hydrochloride Chemical compound Cl.CCC(O)=O YYFIGOPUHPDIBO-UHFFFAOYSA-N 0.000 description 4
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- 125000004494 ethyl ester group Chemical group 0.000 description 3
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- 102000005962 receptors Human genes 0.000 description 3
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- QVWAEZJXDYOKEH-UHFFFAOYSA-N 3-(3-hydroxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC(O)=C1 QVWAEZJXDYOKEH-UHFFFAOYSA-N 0.000 description 2
- UQNKSTVBQXFSDQ-UHFFFAOYSA-N 4-bromo-2,3-dichlorophenol Chemical compound OC1=CC=C(Br)C(Cl)=C1Cl UQNKSTVBQXFSDQ-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 210000003771 C cell Anatomy 0.000 description 2
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- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
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- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
- C07C217/30—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring
- C07C217/32—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
- C07C217/34—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Nutrition Science (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42910502P | 2002-11-26 | 2002-11-26 | |
| PCT/US2003/037461 WO2004047751A2 (en) | 2002-11-26 | 2003-11-25 | Calcilytic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ540275A true NZ540275A (en) | 2007-11-30 |
Family
ID=32393505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ540275A NZ540275A (en) | 2002-11-26 | 2003-11-25 | Calcilytic compounds and their use as calcium receptor antagonists |
Country Status (33)
| Country | Link |
|---|---|
| US (6) | US7514473B2 (no) |
| EP (1) | EP1569892B1 (no) |
| JP (1) | JP4489597B2 (no) |
| KR (2) | KR101142697B1 (no) |
| CN (1) | CN1325466C (no) |
| AP (1) | AP2113A (no) |
| AR (1) | AR042132A1 (no) |
| AU (1) | AU2003291157C1 (no) |
| BR (1) | BR0316544A (no) |
| CA (1) | CA2507226C (no) |
| CO (1) | CO5570664A2 (no) |
| CY (1) | CY1113083T1 (no) |
| DK (1) | DK1569892T3 (no) |
| EA (1) | EA009603B1 (no) |
| ES (1) | ES2388277T3 (no) |
| HK (1) | HK1082914A1 (no) |
| IL (1) | IL168704A (no) |
| IS (1) | IS2897B (no) |
| MA (1) | MA27528A1 (no) |
| MX (1) | MXPA05005574A (no) |
| MY (1) | MY143244A (no) |
| NO (1) | NO332304B1 (no) |
| NZ (1) | NZ540275A (no) |
| OA (1) | OA12962A (no) |
| PE (1) | PE20040845A1 (no) |
| PL (1) | PL211571B1 (no) |
| PT (1) | PT1569892E (no) |
| SI (1) | SI1569892T1 (no) |
| TW (1) | TWI316511B (no) |
| UA (1) | UA81642C2 (no) |
| UY (1) | UY28089A1 (no) |
| WO (1) | WO2004047751A2 (no) |
| ZA (1) | ZA200504104B (no) |
Families Citing this family (7)
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| UY28089A1 (es) | 2002-11-26 | 2004-06-30 | Smithkline Beecham Corp | Compuestos calciliticos |
| US20070155819A1 (en) * | 2004-02-06 | 2007-07-05 | Marquis Robert W Jr | Calcilytic compounds |
| TW200845956A (en) * | 2006-12-18 | 2008-12-01 | Smithkline Beecham Corp | Calcilytic compounds |
| CA2726610C (en) * | 2008-06-05 | 2015-05-05 | Asahi Kasei Pharma Corporation | Sulfonamide compounds and use thereof |
| ES2412408T3 (es) * | 2008-12-24 | 2013-07-11 | Daiichi Sankyo Company, Limited | Compuestos de indanilo |
| GB201217330D0 (en) | 2012-09-28 | 2012-11-14 | Univ Cardiff | Therapeutic for treating inflammatory lung disorders |
| WO2015196205A1 (en) * | 2014-06-20 | 2015-12-23 | Glaxosmithkline Llc | Method of using calcilytic compounds to treat diseases of abnormal glucose or insulin levels |
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| ES442062A1 (es) | 1975-10-24 | 1977-04-01 | Andreu Sa Dr | Procedimiento para la obtencion de 1-ariloxi-2-hidroxi-3- alquilaminopropanos. |
| DE2644833A1 (de) | 1976-10-05 | 1978-04-20 | Boehringer Sohn Ingelheim | Neue 1-aryloxy-2-hydroxy-3-alkylenaminopropane und verfahren zu ihrer herstellung |
| CH618335A5 (no) * | 1977-05-31 | 1980-07-31 | Arnegger Richard E | |
| US4234595A (en) | 1977-07-13 | 1980-11-18 | Mead Johnson & Company | 3-Indolyl-tertiary butylaminopropanols |
| IT1101724B (it) * | 1978-12-05 | 1985-10-07 | Erba Carlo Spa | Derivati morfolinici e fenossiprofanolaminici e procedimento per la loro preparazione |
| IL56369A (en) | 1978-01-20 | 1984-05-31 | Erba Farmitalia | Alpha-phenoxybenzyl propanolamine derivatives,their preparation and pharmaceutical compositions comprising them |
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| ES480066A1 (es) | 1979-04-28 | 1980-04-01 | Especialid Latin Medicam Unive | Procedimiento de obtencion de 1-4-cloro-&,&-dimetil-benceno-etanamino-2-oxi-3 ariloxi propanos. |
| DE3544172A1 (de) | 1985-12-13 | 1987-06-19 | Lentia Gmbh | Neue kristalline salze von aryloxy-propanolaminen, verfahren zu ihrer herstellung und ihre verwendung |
| FR2601008B1 (fr) | 1986-07-03 | 1990-03-30 | Sanofi Sa | Procede de synthese stereospecifique de derives de l'indole |
| DD298506A5 (de) * | 1988-12-30 | 1992-02-27 | Ernst-Moritz-Arndt-Universitaet Greifswald,De | Verfahren zur herstellung halogensubstituierter 1-phenoxy-3-alkylamino-propan-2-ole |
| DE4040186A1 (de) | 1989-12-20 | 1991-06-27 | Hoechst Ag | Hypoglykaemisch aktive propandiolaminderivate mit insulin-aehnlicher wirkung und deren verwendung, neue propandiolaminderivate, diese substanzen enthaltende pharmazeutische zubereitungen und ihre verwendung zur behandlung von krankheiten |
| HN1996000101A (es) | 1996-02-28 | 1997-06-26 | Inc Pfizer | Terapia combinada para la osteoporosis |
| SG99290A1 (en) * | 1996-04-09 | 2003-10-27 | Nps Pharma Inc | Calcilytic compounds |
| US6818660B2 (en) | 1996-04-09 | 2004-11-16 | Nps Pharmaceuticals, Inc. | Calcilytic compounds |
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| US7202261B2 (en) | 1996-12-03 | 2007-04-10 | Nps Pharmaceuticals, Inc. | Calcilytic compounds |
| TW483881B (en) | 1996-12-03 | 2002-04-21 | Nps Pharma Inc | Calcilytic compounds |
| JP2001519813A (ja) | 1997-04-04 | 2001-10-23 | スミスクライン・ビーチャム・コーポレイション | カルシウム溶解性化合物 |
| UY24949A1 (es) | 1997-04-08 | 2001-04-30 | Smithkline Beecham Corp | Compuestos calcilíticos |
| DE19913753A1 (de) | 1998-04-01 | 1999-10-07 | Mannesmann Rexroth Ag | Verfahren zur Bildung des Mittelwertes |
| AR014975A1 (es) | 1998-04-08 | 2001-04-11 | Nps Pharma Inc | Compuestos calciliticos, una composicion farmaceutica que los comprende, y el uso de los mismos para la fabricacion de un medicamento |
| AR018177A1 (es) | 1998-04-08 | 2001-10-31 | Smithkline Beecham Corp | Compuestos calciliticos, una composicion farmaceutica que los comprende y el uso de los mismos para la manufactura de un medicamento. |
| US6335338B1 (en) | 1998-08-12 | 2002-01-01 | Smithkline Beecham Corporation | Calcilytic compounds |
| EP1112073A4 (en) | 1998-08-12 | 2002-10-25 | Smithkline Beecham Corp | CALCILYTIC COMPOUNDS |
| PE20001456A1 (es) | 1999-02-02 | 2001-01-28 | Smithkline Beecham Corp | Compuestos calcioliticos |
| WO2001007026A2 (en) | 1999-07-22 | 2001-02-01 | Eli Lilly And Company | Improved method of treating type ii diabetes and obesity |
| ECSP003590A (es) | 1999-07-31 | 2002-02-25 | Smithkline Beecham Corp | Compuestos calcioliticos |
| US20030018203A1 (en) | 2002-07-17 | 2003-01-23 | Largo Maria Amparo | Calcilytic compounds |
| MY159417A (en) * | 2000-01-24 | 2017-01-13 | Smithkline Beecham Corp | Calcilytic compounds |
| BR0112600A (pt) | 2000-07-21 | 2003-06-24 | Smithkline Beecham Corp | Compostos calcilìticos |
| CZ20031144A3 (cs) | 2000-10-25 | 2004-08-18 | Smithklineábeechamácorporation | Kalcilytické sloučeniny |
| ES2273909T3 (es) | 2000-10-25 | 2007-05-16 | Smithkline Beecham Corporation | Compuestos calciliticos. |
| AU2002254136A1 (en) | 2001-03-08 | 2002-09-24 | Smithkline Beecham Corporation | Pcra helicase inhibitors |
| US6864267B2 (en) | 2001-07-16 | 2005-03-08 | Smithkline Beecham Corporation | Calcilytic compounds |
| UY28089A1 (es) | 2002-11-26 | 2004-06-30 | Smithkline Beecham Corp | Compuestos calciliticos |
| ATE489368T1 (de) | 2003-04-07 | 2010-12-15 | Nps Pharma Inc | Pyrimidinonverbindungen als calcilytica |
| US20070010571A1 (en) | 2003-08-20 | 2007-01-11 | Nitromed, Inc. | Nitrosated and nitrosylated cardiovascular compounds, compositions and methods of use |
| TW200524892A (en) | 2003-09-24 | 2005-08-01 | Glaxo Group Ltd | Calcilytic compounds |
| WO2005030746A1 (en) | 2003-09-24 | 2005-04-07 | Glaxo Group Limited | Calcilytic compounds |
| EP1713767A4 (en) | 2004-02-06 | 2008-01-16 | Smithkline Beecham Corp | CALCILYTIC COMPOUNDS |
| NL1025457C1 (nl) | 2004-02-11 | 2005-08-12 | Rudolf Johannes Gerardus Hoorn | Haspelrem. |
| CA2576279A1 (en) | 2004-11-08 | 2006-05-18 | Nitromed, Inc. | Nitrosated and nitrosylated compounds, compositions and methods for the treatment of ophthalmic disorders |
| EP1846380A4 (en) | 2005-01-21 | 2010-02-17 | Nicox Sa | HETEROCYCLIC NITROGEN MONOXIDE DONOR COMPOSITIONS CONTAINING CARDIOVASCULAR COMPOUNDS, AND METHODS OF USING THE SAME |
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- 2003-11-24 MY MYPI20034511A patent/MY143244A/en unknown
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- 2003-11-25 KR KR1020117025893A patent/KR101142697B1/ko not_active IP Right Cessation
- 2003-11-25 OA OA1200500152A patent/OA12962A/en unknown
- 2003-11-25 DK DK03783752.3T patent/DK1569892T3/da active
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- 2003-11-25 PL PL376965A patent/PL211571B1/pl unknown
- 2003-11-25 PT PT03783752T patent/PT1569892E/pt unknown
- 2003-11-25 EP EP03783752A patent/EP1569892B1/en not_active Expired - Lifetime
- 2003-11-25 NZ NZ540275A patent/NZ540275A/en not_active IP Right Cessation
- 2003-11-25 PE PE2003001196A patent/PE20040845A1/es not_active Application Discontinuation
- 2003-11-25 SI SI200332179T patent/SI1569892T1/sl unknown
- 2003-11-25 MX MXPA05005574A patent/MXPA05005574A/es active IP Right Grant
- 2003-11-25 EA EA200500878A patent/EA009603B1/ru not_active IP Right Cessation
- 2003-11-25 ES ES03783752T patent/ES2388277T3/es not_active Expired - Lifetime
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- 2003-11-25 JP JP2004555635A patent/JP4489597B2/ja not_active Expired - Fee Related
- 2003-11-25 BR BR0316544-2A patent/BR0316544A/pt active Search and Examination
- 2003-11-25 KR KR1020057009379A patent/KR20050086786A/ko not_active Application Discontinuation
- 2003-11-25 WO PCT/US2003/037461 patent/WO2004047751A2/en active Application Filing
- 2003-11-25 CN CNB2003801092068A patent/CN1325466C/zh not_active Expired - Fee Related
- 2003-11-25 US US10/536,416 patent/US7514473B2/en not_active Expired - Fee Related
- 2003-11-25 UA UAA200505005A patent/UA81642C2/ru unknown
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- 2005-05-19 IL IL168704A patent/IL168704A/en not_active IP Right Cessation
- 2005-05-23 MA MA28294A patent/MA27528A1/fr unknown
- 2005-05-24 CO CO05050416A patent/CO5570664A2/es active IP Right Grant
- 2005-06-02 IS IS7880A patent/IS2897B/is unknown
- 2005-06-22 NO NO20053071A patent/NO332304B1/no not_active IP Right Cessation
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- 2006-02-07 ZA ZA200504104A patent/ZA200504104B/en unknown
- 2006-03-02 HK HK06102773.3A patent/HK1082914A1/xx not_active IP Right Cessation
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2009
- 2009-02-26 US US12/393,284 patent/US7829594B2/en not_active Expired - Fee Related
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- 2010-09-30 US US12/894,644 patent/US8399517B2/en not_active Expired - Fee Related
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2012
- 2012-09-03 CY CY20121100784T patent/CY1113083T1/el unknown
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2013
- 2013-02-11 US US13/764,126 patent/US8586631B2/en not_active Expired - Fee Related
- 2013-11-01 US US14/069,447 patent/US8980950B2/en not_active Expired - Fee Related
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2015
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